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亚型选择性烟碱激动剂增强正常大鼠嗅觉工作记忆:气味跨度任务的新用途。

Subtype-selective nicotinic agonists enhance olfactory working memory in normal rats: a novel use of the odour span task.

机构信息

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.

出版信息

Neurosci Lett. 2010 Mar 3;471(2):114-8. doi: 10.1016/j.neulet.2010.01.022. Epub 2010 Jan 18.

Abstract

Nicotinic agonists have been shown to enhance performance in cognitive tasks based on attention and memory. The aim of this study was to use a test of olfactory working memory; the odour span task (OST) in rodents, to investigate the effects of subtype-specific nicotinic agonists on working memory in normal rats. Rats were trained in a non-matching to sample (NMTS) rule and then the full OST, which involved identifying a novel odour from an increasing number of presented odours. Male hooded Lister rats were treated with nicotine, selective nicotinic agonists or vehicle (saline). In order to validate the task, muscarinic and nicotinic receptor antagonists were also examined. Nicotine at both 0.05 and 0.1mg/kg significantly increased mean span length in the OST. The selective alpha 4 beta 2 nicotinic receptor agonist metanicotine (0.1mg/kg s.c.) and the selective alpha 7 nicotinic receptor agonist (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A, 10mg/kg i.p.) also improved performance. In contrast, mecamylamine and scopolamine significantly decreased mean span length. These findings suggest a role for the activation of both alpha 4 beta 2 and alpha 7 subtypes of neuronal nicotinic receptor in mediating enhancements of olfactory working memory capacity in normal, non-compromised rats. These nicotinic receptor subtypes may therefore prove to be useful targets for the development of novel treatments for neuropsychiatric disorders that involve cognitive dysfunction.

摘要

烟碱型乙酰胆碱受体激动剂已被证明可增强基于注意力和记忆的认知任务的表现。本研究旨在使用嗅觉工作记忆测试;即气味跨度任务(OST)在啮齿动物中,研究特定亚型烟碱受体激动剂对正常大鼠工作记忆的影响。大鼠在非匹配样本规则(NMTS)中接受训练,然后进行完整的 OST,其中包括从越来越多呈现的气味中识别新气味。雄性 Hooded Lister 大鼠接受尼古丁、选择性烟碱受体激动剂或载体(盐水)治疗。为了验证该任务,还检查了毒蕈碱和烟碱受体拮抗剂。尼古丁在 0.05 和 0.1mg/kg 时均显著增加了 OST 的平均跨度长度。选择性α4β2烟碱受体激动剂甲尼克定(0.1mg/kg sc)和选择性α7烟碱受体激动剂(R)-N-(1-氮杂双环[2.2.2]辛-3-基)(5-(2-吡啶基)噻吩-2-甲酰胺)(化合物 A,10mg/kg ip)也改善了性能。相比之下,美金刚和东莨菪碱显著降低了平均跨度长度。这些发现表明,激活α4β2 和α7 型神经元烟碱受体亚型在介导正常、未受损大鼠嗅觉工作记忆能力增强方面发挥作用。因此,这些烟碱受体亚型可能被证明是开发涉及认知功能障碍的神经精神疾病新型治疗方法的有用靶点。

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